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Received: 30 April 2020    Revised: 26 May 2020    Accepted: 28 May 2020

DOI: 10.1111/jocd.13531

REVIEW ARTICLE

Why we should be avoiding periorificial mimetic muscles when

injecting tissue fillers

Greg J. Goodman MBBS, FACD, MD1,2,3  | Firas Al-Niaimi MSc, MRCP, EBDV4,5,6  |

Cara McDonald MBBS, MPH, FACD7 | Antoinette Ciconte MBBS, FACD8 |
Catherine Porter MBBS9

1
Monash University, Carlton, Vic., Australia
2 Abstract
Skin Health Institute, Carlton, Vic.,
Australia Background: Tissue fillers are generally safe and well tolerated by patients. However,
3
University College of London, London, UK complications do occur and may be very severe, such as intravascular injection (with
4
Guy’s Hospital London, London, UK occasional residual tissue loss, visual and neurological sequelae) and late nodularity
5
152 Harley Street Clinic, London, UK
6
and swelling. Methods to lessen the likelihood of complications have been the sub-
Department of Dermatology, Aalborg
University Hospital, Aalborg, Denmark ject of much recent literature. Depth of injection has been identified as a key safety
7
St Vincent’s Hospital Fitzroy, Fitzroy, Vic., consideration.
Australia
Patients/Methods: The role of injection of facial filler into the muscular layer of the
8
Box Hill Hospital, Box Hill, Vic., Australia
9
face is explored in this article. Literature was explored using available search facilities
All Saints Clinic, Double Bay, NSW,
Australia to study the role of injections in or around this layer in the production of significant
adverse reactions.
Correspondence
Greg J. Goodman, Dermatology Institute of Results: A body of literature seems to suggest that injection into mimetic muscula-
Victoria, 8-10 Howitt St South Yarra 3141, ture of the face especially the musculature in the periorbital and perioral regions is
Victoria, Australia.
Email: gg@div.net.au prone to adverse reactions.
Conclusions: Injection of agents into the perioral and periorbital mimetic muscular
layer may produce, product clumping, displacement, and tendency to late nodularity
and swelling. It also risks intravascular injection as compared to injection of other lay-
ers of the face. Injection into the mimetic muscles especially the sphincteric muscles
should be avoided to minimize the risk of complications.

KEYWORDS

COVID-19, mimetic muscles, orbicularis oculi, orbicularis oris, Tissue fillers

1 | I NTRO D U C TI O N 2 | A DV E R S E R E AC TI O N S

The burgeoning use of filling materials has brought with it an increas- Adverse reactions to filler materials may be divided into vascular1,2
ing interest in safety aspects of these agents. Although well-toler- and nonvascular issues.3,4
ated in general, there are serious albeit rare adverse reactions that The vascular issues have been well-described. They consist of
demand attention. the following:

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction
in any medium, provided the original work is properly cited and is not used for commercial purposes.
© 2020 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC

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1846     
wileyonlinelibrary.com/journal/jocd J Cosmet Dermatol. 2020;19:1846–1850.
GOODMAN et al.
• Minor bruising and ecchymosis from transient contact with or
puncture of the prevailing vasculature
• True intravascular injection and embolization of fillers with tissue
ischemia in the angiosome distribution of the vascular occlusion. 5
Dependent on the exact anatomy of the obstruction, tissue loss
may be cutaneous only and/or involve deeper structures
• Distant embolization of fillers, in some individuals, may result in
partial or complete unilateral and rarely bilateral visual loss and
neurological deficit
Nonvascular issues may include:
• Misplacement or over correction often by poor injection tech-
nique or product choice
• Inadvertent placement into the retroorbital space
• Migration of a high G prime filler from the cheek into the tear
trough region.
• Frank sepsis, which is serious but rare and usually seen in the con-
text of a break in sterile technique or patient-related factors such
as poor local barrier function with altered local skin microbiome
Recently, the problem of delayed or late reactions to fillers has
been more frequently reported and has been the subject of multiple
consensus documents. These reactions include the following:
• Late noninflammatory appearing nodules/swelling- occasionally
filler material—especially in the infraorbital zone sometimes many
years post filler injection. Many theories have been asserted for
this late occurrence, but most rely on the interplay of the orbicu-
laris function and the lack of natural dissolution of product in the
periorbital area
• Evanescent and sometimes recurrent noninflammatory and in-
flammatory reactions appearing at times of heightened immune
activity such as viral infections, which are common in both perior-
bital and perioral regions
• More fixed and problematic noninflammatory and inflammatory
reactions which may arise weeks or months post injection. These
would appear to be an interplay between the presence and me-
tabolism of the filler, infection, and host inflammation. It is prob-
able that host factors influence all of these with the reaction to
infection, extent of the inflammatory reaction and the metabo-
lism of the filler all possibly varying in different individuals
3 |  TH E PE R I O R A L A N D PE R I O R B ITA L
M U S C U L AT U R E
The orbicularis muscles surrounding the eyes and the mouth are similar
in many respects. They both function to maintain or coordinate open-
ing and closing functions of the eyes and mouth, and they both con-
tribute to nonverbal communication and age determination, through
their insertion into the dermis for expression and wrinkle production.
They both fuse and coordinate with surrounding muscles to enable the
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multiple coordinated actions required for their basic functions as well
as their role in expressions in both verbal and nonverbal forms.
They differ in a number of aspects. The orbicularis oculus mus-
cle is more of a true sphincteric muscle.6 Its functions are to close
the eyelid and assist in pumping the tears into the nasolacrimal
system. The orbicularis oculus muscle is a large muscle with three
components. The outermost is the orbital component under volun-
tary control to allow expressions such as closing the eye, winking
and smiling, the next section moving inward toward the eye is the
pre-septal component which functions to squeeze the eyes shut ei-
ther by voluntary or involuntary blink response means and the in-
nermost pre-tarsal that keeps the eyelids opposed during sleep. The
orbital component attaches medially to the medial canthal tendon
and periosteum whereas the pre-septal and pre-tarsal components
divide medially into deep and superficial heads before insertion.
Laterally, the muscle attaches to the lateral canthal tendon, raphe,
and surrounding tissues.
The orbicularis oris muscle has no periosteal or bony insertions
and is not a true sphincteric muscle being made of four cooperating
quadrants. It also has two layers—a deep layer acting as a constrictor
cooperating in mastication and the superficial muscle layer related
to speech and facial expressions. Much of the attachment of the
orbicularis oris is to the modiolus bilaterally and to the muscles of
expression for the superficial component.7
4 | M E TH O DS
Literature search databases (PubMed, Ovid, and Google Scholar)
were examined for articles on mimetic muscles, intramuscular injec-
tions and fillers, and filler reactions and combinations and variations
of these terms. The anatomy of the periorbital and perioral zones
was also searched and explored to assess any unusual aspects of
these sphincter muscles that may contribute to adverse issues.
5 | R E S U LT S
Results from these searches raised some concerns about adverse
reactions both by the possibility of intravascular injection and ex-
travascular reactions and repositioning of product relating to inject-
ing filler materials into the mimetic muscles.
6 | D I S CU S S I O N
The issues with the muscular layer and fillers.
6.1 | Vascular issues
These periorificial muscles are dynamic and very active mus-
cles. They have abundant blood supply and important vascular
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1848       GOODMAN et al.
connections. This is seen by the frequency of bruising on inject-
ing either around the eyes and the mouth. In the perioral area, the
large vessels of the inferior and superior labial arteries along with
the mental and submental all are potential embolic targets.8,9 These
tend to run either just superior or inferior to the muscles of the
perioral region. There is much variability of vascular architecture
within the horizontal layer but far less variability in their depth. It
is thus advisable to keep away from these structures by gleaning
an understanding of vascular anatomy in each area of injection and
maintaining a respectful distance from major vessels. However, even
depth is imperfect, with variability in the superior labial artery from
its usual plane in greater than 20% of cadavers10 being between the
orbicularis muscle and the mucosa in 78%, between the superficial
and deep parts of the orbicularis muscle in 17.5% and superficial to
the muscle (between the skin and the orbicularis muscle in 2.1%). As
the vessels tend to track the muscles rather intimately, keeping clear
of these structures would seem prudent. A notable exception to this
variation of vascular anatomy and where depth is fixed pertains to
the emergence of the supratrochlear, supraorbital, zygomaticofacial,
zygomaticotemporal, infraorbital, and mental arteries through their
foramina. These regions should be avoided at depth or approached
in a fashion to minimize the chance of intravascular injection. Around
the eyes, vascular supply emanates from the facial and superficial
temporal as well as the ophthalmic arteries.11 Similarly, it is usually
advised around the eyes that deep injection below the muscular
layer or superficial injection above it are safer options than intra-
muscular injections. However, medially in the tear trough, this is not
practical as the muscle is tightly bound to the periosteum.12
6.2 | Mechanical effects
The periorificial muscles act as squeezing muscles closing their ori-
ficial structures. Any material implanted in these structures is likely
to be displaced. This may lead to anterior displacement of product
in the infraorbital zone if it is placed into the muscles. Added to this,
injection even if intended to be deep may in fact be intramuscular in
this zone.13,14 In the perioral zone, constant muscle movement, which
cannot be prevented during speech and mastication, can compress
an injected linear strand to a lump. Therefore, intramuscular injection
may lead to clumping and increase the chance of nodule formation
with Poly-L-Lactic Acid. The incidence appears to be reduced when
the perioral and periorbital zones are avoided.15,16 It is suggested
by manufacturers of Calcium hydroxyapatite and acrylate fillers that
the regions around the eyes and mouth are not targeted.17,18 It is un-
known at this time whether the higher incidence of clumping or nod-
ules with these products is because the intramuscular injection is
specifically the risk or the higher movement or metabolic activity of
these areas or other the effect of unknown factors. Autologous fat
injection into muscles was a technique described close to 20 years
ago but has not been described often over recent years.19,20
In addition, the muscles of facial expression lack an envelop-
ing fascia, that is, epimysium with the exception of the buccinator
muscle. Furthermore, most of the facial muscles change planes from
layer 5 to layer 2 in the face. 21 Thus theoretically, the filling sub-
stance may not remain contained within the muscle where initially
placed but may over time end up in multiple planes or extruded from
the muscle.
6.3 | Metabolic effects
The metabolic activity inherent in the musculature and its support-
ing vasculature may support vigorous inflammatory responses once
initiated. A strict sterile, or clean environment, is difficult to maintain
in the perioral zone prior to, during, and after procedure, and intro-
duction of bacteria is likely with all injections. It is probable that the
periphery of the filler injected is what is subjected initially and over
time to degradative forces via specific enzymes such as hyaluroni-
dase and reactive oxygen species via inflammation. The continual
mechanical distortion of boluses of material may break down larger
clumps of fillers exposing them to more metabolic activity and po-
tential inflammatory effects.
6.4 | Specific use of hyaluronic acid fillers
As most injections in these regions are now hyaluronic acid, it is use-
ful to look at the recent literature in relation to delayed nodules with
these agents. Both regions are susceptible to late nodule develop-
ment with this agent.
The preceding discussion is very pertinent to these agents. It
is likely that over time the following may occur. Over the weeks or
months after injection, a bolus of hyaluronic acid (HA) filler may
be expected to be degraded on the periphery of the bolus by local
enzymatic activity and inflammatory mediators. All HA filler ma-
terials start as high molecular weight hyaluronic acid compounds
(>1000 kDa). Some fillers have lower hyaluronic HA (>500 kDa) in
combination with high molecular weight HA but even this is far away
from low molecular weight HA (10-250 kDa). Low molecular weight
HA (10-20 kDa) is the eventual breakdown product of all HA prod-
ucts, and if this occurs at a normal rate, it will be seen as gradual loss
of filler volume over time.
Current observation shows that a bolus of filler if implanted
within muscle may follow a different cascade. Over time, the
periphery will be exposed to normal metabolic degradation, but
mechanical effects may induce change in, or magnification of the
filler surface area over time. In one study, 5 of 7 explanted facial
implants demonstrated biofilm formation under electron micros-
copy, and rougher, more porous surfaces displayed more severe
biofilm formation than smoother implants. Theoretically, this
could be extrapolated to HA filler in the above circumstance. 22,23
In the presence of either implanted bacteria or hematogenous de-
rived pathogens at the periphery of the filler, the resultant inflam-
mation to this infection will cause accelerated degradation of the
HA filler to low molecular weight hyaluronic acid. Low molecular
GOODMAN et al.
weight HAs are pro-inflammatory and may create a feedback loop
inducing further inflammation. A case report describes progres-
sively worsening eyelid edema with histopathological evidence
of degenerating striated muscle surrounding pools of hyaluronic
acid. 24 Chronic inflammation or toxicity secondary to filler break-
down products were put forward as possible explanations . 25,26
Certain HA agents may be more prone to this activation than
others. Certain patients may be able to mount reactions more
significantly than other patients and the infective agent will il-
licit differing effects depending on its relative virulence. Injecting
into muscles is likely in both the periorbital and perioral zones
to create a suitable environment amplifying the likelihood of this
activity.
6.5 | Injecting the perioral and periorbital zones
To decrease the rate of delayed nodules in these areas, it is best to
lay down very small aliquots or layers that may be more difficult to
clump or alter with mechanical movement. It is advisable to inject
slowly to decrease trauma to the tissues and to avoid intravascu-
lar injection. It is imperative that sterility is maximized especially in
the perioral area. This includes complete face washing and recurrent
use of antiseptics locally throughout the injection process. It may be
that in the current COVID-19 pandemic that use of mouth, nose, and
eye antiviral irrigation may become commonplace. From the fore-
going discussion, avoiding the muscular layer is also recommended.
All this becomes more important when using certain product lines.
HA products are possibly not all the same. Some may have a higher
rate of issues than others and many may have a higher rate of issues
when introduced to a market than they do after market experience.
In jurisdictions where teaching has been to avoid the muscular layer,
large boluses and rapid injections the complication rate appears to
be less.
6.6 | COVID-19 and periorificial treatment
There is now an additional confounder for injecting in the perioral
and periorbital zone, the risk of contamination in a patient carrying
or presymptomatic of COVID-19. Although not common, COVID-
19 has been found in ocular secretions with reports of ophthal-
mologists and otolaryngologists dying of coronavirus. 27 The nose
and surrounding zones and the mouth and perioral area are more
concerning 28 especially as fillers in these areas are so common.
Treatment of these areas may be problematic at this time but if
they are attempted, decreasing viral load with mouth rinses and
nasal applications may be an important consideration. 29
ORCID
Greg J. Goodman  https://orcid.org/0000-0003-4089-9690
Firas Al-Niaimi  https://orcid.org/0000-0002-0684-4322
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      1849
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How to cite this article: Goodman GJ, Al-Niaimi F, McDonald
C, Ciconte A, Porter C. Why we should be avoiding periorificial
mimetic muscles when injecting tissue fillers. J Cosmet
Dermatol. 2020;19:1846–1850. https://doi.org/10.1111/
jocd.13531